Tetrahydrofuran polycarboxylates

ABSTRACT

A compound of the formula ##STR1## wherein R&#39; is lower alkyl is useful as an intermediate to prepare a compound of the formula ##STR2## wherein X is selected from the group consisting of: ##STR3## wherein R is selected from the group consisting of alkali metal, NH 4   + , NH(CH 2  CH 2  OH) 3   + , and lower alkyl, branched or straight chain, with up to about C 20  in the chain. The esters can be converted to salts useful as detergent builders.

This is a division of application Ser. No. 756,946, filed Jan. 5, 1977,now U.S. Pat. No. 4,120,874.

The present invention relates to a process for preparing compounds ofthe molecular structure represented by the formula: ##STR4## wherein Xis selected from the group consisting of: (A) WHERE THE COMPOUNDS ARETETRAHYDROPYRAN TYPE COMPOUNDS ##STR5## (b) where the compounds are1,4-dioxane type compounds: ##STR6## and (C) WHERE THE COMPOUNDS ARETETRAHYDROFURAN TYPE COMPOUNDS: ##STR7## WHEREIN R is selected from thegroup consisting of alkali metal, ammonium, trialkanolammonium, andlower alkyl, branched or straight chain, with up to about C₂₀ in thechain, comprising:

(a) preparing a suitable halo dicarboxy ester of an aldehyde of thegeneral formula ##STR8## wherein M is halogen, X is as defined above,and R' is lower alkyl, preferably ethyl or methyl.

(b) cyclizing the compound of (a) to the cyclic cyano diesterintermediate of the formula: ##STR9## wherein X and R' are as givenabove, and (c) hydrolyzing the intermediates to Step (b) to thecorresponding salts, and if desired, converting the salts to thecorresponding triesters or acids.

The salt compounds produced in accordance with the process of thepresent invention have utility as water softeners, detergent builders,calcium and magnesium sequestrants, scale dissolvers, and the like. Thecompounds may be used alone or as additives to a variety of solid orliquid detergent formulations. In such formulations the compoundsenhance the cleaning capacity of the detergent by providing a builder,threshold or other effect. The esters are useful in synthesizing thepure salt forms of the compounds. The cyclic cyano diester intermediatesare useful in preparing the end product tri-salts, esters or acids.

DESCRIPTION OF THE PRIOR ART

The preparation of some of the compounds within the scope of the generalformula set forth above is described in U.S. Pat. application Ser. No.765,947 filed Jan. 5, 1977 in the names of Marvin M. Crutchfield andCharles J. Upton. In that application the inventors describe a processfor producing compounds, such as the trisodium andtriester-2,2,6-tetrahydropyran-tricarboxylates by a process of basiccarboxylation to produce the partial esters followed by hydrolysis tothe salt forms. The salts in turn are capable of being esterified to thecorresponding full esters.

The present invention comprises a novel and highly effective route tothe synthesis of the subject compounds which is entirely dissimilar tothe phenate carboxylation approach taken by Crutchfield and Upton.

SUMMARY OF THE INVENTION

The invention provides a highly effective method for synthesizingcompounds having a molecular structure represented by the formula:##STR10## wherein X and R are as described above.

The method for preparing the subject compounds generally comprises,

(a) preparing a suitable halo dicarboxy ester of an aldehyde of thegeneral formula ##STR11## wherein M is halogen, and R' is lower alkyl,preferably ethyl or methyl. (b) cyclizing the compound of (a) to formthe cyclic diester intermediate of the formula: ##STR12## wherein X andR' are as described above, (c) hydrolyzing the intermediates of Step (b)to the corresponding salts, and

(d) if desired, esterifying the salts of Step (c) to the correspondingesters.

Among the preferred compounds (and intermediates) of the above generalformula which may be prepared in accordance with the present process,are the following: ##STR13##

in the above formulae R is as described above, but is preferably CH₃ orC₂ H₅ for the cyano intermediate compound and H, Na, CH₃ or C₂ H₅ forthe end product compound.

DETAILED DESCRIPTION OF THE INVENTION

A detailed description of the process of the present invention isembodied in the following illustrative working examples.

EXAMPLE 1 Preparation of Trisodium 2,2,6-Tetrahydropyrantricarboxylate(a) Preparation of γ-Chlorobutyraldehyde Diethyl Acetal

The named compound was prepared by the method of Loftfield, J. Am. Chem.Soc., 73 1365 (1951), with minor modifications, according to thefollowing general reactions: ##STR14##

In carrying out this step of the preparation of 3l baffled 3-neck, roundbottom flask was fitted with a gas dispersion tube, mechanical stirrerand reflux condenser. The flask was charged with 282g (2 moles) ofγ-chlorobutyryl chloride, 1450 ml toluene, 30g of 5% Pd/BaSO₄, and 3.1ml of quinoline/sulfur catalyst poison (catalyst poison was prepared byrefluxing 1g sulfur with 6g quinoline for 5 hours and diluting to 70 mlwith xylene). Hydrogen was then bubbled through the stirred reactionmixture and the temperature raised to reflux. The off-gases were bubbledinto a 2l flask containing 1.5l water. 5N NaOH was added to neutralizethe HCl as it was given off. After 3 hours, HCl evolution had stoppedand the reaction mixture was allowed to cool at room temperature under aN₂ atmosphere.

A solution of 200g CaCl₂ in 1250 ml abs. EtOH was added and the stirringwas continued overnight. The reaction mixture was filtered to remove thecatalyst and the filtrate was washed with 800 ml water and 2× 400 ml 5%NaHCO₃ solution. The aqueous phases were combined and extracted with 500ml toluene. The organic phases were combined and washed with 400 ml 5%NaHCO₃, 400 ml saturated NaCl and dried over anhydrous K₂ CO₃. Themixture was filtered and the bulk of the toluene was removed on a rotaryevaporator. The crude product was then distilled through an 18" silveredvacuum jacketed column packed with Berl saddles. The product (283g) wascollected at 83°-4° at water aspirator pressure (89°-92°/14mm). This isa 78% yield based on raw materials. A later similar run gave 81%. 'H nmrwas consistent with the structure.

(b) Preparation of δ,δ-Dicarbethoxyvaleraldehyde Diethyl Acetal

The named compound was prepared by reacting the γ-chlorobutyraldehydediethyl acetal prepared in accordance with Step (a), above, with sodiumdiethyl malonate according to the following reaction: ##STR15##

To carry out the foregoing preparation 168g (1.05 mole of diethylmalonate and 15g (0.1M) NaI were added to a solution of 23g (1M) of Nametal dissolved in 750 ml ethanol. After about 5 minutes at 50° C., 190g(1.05M) of γ-chlorobutyraldehyde diethyl acetal was added. Thetemperature was raised to reflux and after 1.5 hours an additional 80g(0.5M) of diethyl malonate was added. The reaction mixture was refluxedovernight. The next day glc indicated unreacted acetal, so additionalNa/EtOH was added and the mixture was refluxed for 3 more hours. Theethanol was then removed on a rotary evaporator and the residue taken upin a mixture of 200 ml H₂ O and 200 ml ether. The layers were separatedand the ethereal layer was washed with 2× 200 ml 5% NaHCO₃. The aqueouswashes were combined with the original aqueous layer and extracted with200 ml ether. The ethereal solutions were combined and washed with 5%NaHCO₃ and saturated NaCl. After drying over K₂ CO₃ and removing theether on a rotary evaporator, 366g of 60-70% pure product remained.

This crude product was distilled under vacuum and the product collectedat 115°-124° at 0.1mm Hg. The product (223g, 70% yield) gave a 'H nmrconsistent with the structure.

(c) Preparation of δ-Bromo-δ,δ-Dicarbethoxyvaleraldehyde Diethyl Acetal

The named compound was prepared by reactingδ,δ-dicarbethoxyvaleraldehyde diethyl acetal as prepared in Step (b)with sodium ethoxide and then reacting the resulting sodium compoundwith bromine according to the following reactions: ##STR16##

These reactions were carried out in the following manner:

To a slurry of 45g 50% NaH (washed with 4× 100 ml pentane) in 750 ml DMFwas added 259g of the diethyl acetal of Step (b) and 4.5 ml ethanol. Themixture was stirred at <25° for 2 hours and then an additional 4.5 mlEtOH was added. Since this caused increased H₂ evolution, the mixturewas stirred an additional 6 hours, after which 9 more ml of EtOH wereadded. The reaction mixture was cooled to about 10° and a solution of144g Br₂ in 200 ml DMF was added while the temperature was maintained at<15°. The reaction mixture was allowed to stir overnight at roomtemperature.

The reaction mixture was diluted with 1l of H₂ O and extracted with 3×ll benzene. The benzene exxtracts were washed with 2× 1l H₂ O and 2× 1lsaturated NaCl. The benzene was removed on a rotary evaporator leaving135g crude product which by glc was about 85% pure. The 'H nmr was inagreement with the structure. Experience with a previous run had shownthat decomposition occurred during distillation so this material wasused without further purification.

The choice of DMF as a solvent for this step was not optimum since DMFreacts with NaOEt as evidenced by the presence of considerable amountsof dimethyl amine at the time of the Br₂ addition.

(d) Preparation of δ-Bromo-δ,δ-Dicarbethoxyvaleraldehyde

The named compound was prepared by the hydrolysis of the diethyl acetalprepared in accordance with Step (c), above, by the following reaction:##STR17##

In this step a solution of 305g of crude diethyl acetal in 300 mlbenzene was stirred overnight at room temperature with 2.5l of 4N HCl.The reaction mixture was extracted with 5× 500 ml benzene. The benzeneextracts were washed with 1× 500 ml H₂ O, 2× 500 ml 5% NaHCO₃, and 2×500 ml saturated NaCl. The solution was dried over CaSO₄ and the benzeneremoved on a rotary evaporator having 240g of crude product. The 'H nmrwas consistent with the structure. The material was used without furtherpurification.

(e) Preparation of Diethyl 6-cyano-2,2-tetrahydropyran dicarboxylate

The named compound was prepared by cyclizing the aldehyde prepared inaccordance with Step (d) supra, using sodium cyanide in dimethylsulfoxide according to the following reaction: ##STR18##

To a slurry of 50g NaCN in 700 ml DMSO was added 222g crude aldehyde in80 ml DMSO. The temperature rose spontaneously to 65° at which it washeld by controlling the rate of addition of VI.

The temperature was then held at 65° for an additional 4 hours.

The reaction mixture was diluted with 1.5l H₂ O and extracted with 6×500 ml benzene. The combined extracts were washed with 500 ml saturatedNaHSO₃, 2× 500 ml 5% NaHCO₃, 3× 500 ml saturated NaCl and then driedover CaSO₄. The benzene was removed on a rotary evaporator having 145gcrude product about 50-55% pure.

After several vacuum distillations 65g of 98% pure product was obtained.B.p. 119-121 mm Hg. The 'H nmr was consistent with the structure.

(f) Preparation of Trisodium 2,2,6-Tetrahydropyrantricarboxylate

The named compound was prepared by hydrolysis of the6-cyano-2,2-tetrahydropyrandicarboxylate prepared in accordance withStep (e) above, by the following reaction: ##STR19##

To a solution of 81g of 50% NaOH and 80 ml H₂ O still warm from mixingwas added a solution of 65g of VII in 200 ml MeOH. After stirringovernight at room temperature the solution was warmed to insure thatammonia evolution had ceased. When no ammonia could be smelled, thesolution was allowed to cool and stand overnight at room temperature.This solution was poured into MeOH and an oil was obtained whichsolidified on further treatment with MeOH as the trisodium salt.

(g) Preparation of Triethyl 2,2,6-Tetrahydropyrantricarboxylate (IX)

The named compound was prepared by esterification of the trisodium saltof Step (f). The salt was added to a solution of 600 ml of ethanol and160 ml acetyl chloride and refluxed for 3 hours. The excess HCl wasneutralized by adding solid NaHCO₃ and water until CO₂ evolution ceased.Additional H₂ O was added until almost all of the solids had dissolved.The aqueous solution was then extracted with 3× 500 ml benzene. Theextracts were washed with 300 ml 5% NaHCO₃ and 2× 300 ml saturated NaCland filtered. Most of the benzene was removed on a rotary evaporator andthe residue dried over CaSO₄. The remaining benzene was removed and theresidue (50g) was found to be 95% pure. This was vacuum distilled togive a 30.6g fraction which was 97% pure. Other fractions of 93-95%purity were also obtained but not combined with the purest cut. The 'Hnmr and IR were identical to those obtained for material prepared by thephenate carboxylation route employed by Crutchfield and Upton anddescribed in previously identified Application Ser. No. 765,947.

EXAMPLE 2.

Ammonium, triethanolamine, other soluble alkali metal salts, and theacid form of the cyclic tricarboxylate compounds of this invention areprepared by passing an aqueous solution of the corresponding sodium saltthrough a column of cationic exchange resin charged with the desiredcation, followed by isolation of the salt from the aqueous solution byevaporation or crystallization.

EXAMPLE 3.

The trisodium 2,2,5-tetrahydrofurantricarboxylate may be prepared asfollows:

(a) Preparation of γ,γ-dicarbethoxybutyraldehyde

First, 100 ml acrolein was added to a solution of 180g diethylbromomalonate, 14g tributylamine, and 600 ml ethanol while cooling in anice bath. After 2-3 hours, an additional 1.5g tributylamine and 20 mlacrolein was added. The stirring was continued for an additional 1 to 2hours without additional cooling. The reaction mixture was neutralizedwith 7 ml glacial acetic acid and the ethanol and unreacted acroleinwere removed on a rotary evaporator. The residue was diluted with 500 mlbenzene and washed with 3× 100 ml H₂ O and 2× 100 ml saturated NaClsolution. The benzene solution was dried over CaSO₄ and rotaryevaporated to yield 207g of yellow oil which was indicated to be 48%product by glc.

(b) Preparation of 4-cyano-2,2-dicarbethoxytetrahydrofuran

To a slurry of 30g of NaCN in 500 ml dimethylsulfoxide (DMSO) was addeda solution of 150g of the crude bromoaldehyde product of Step (a) in 100ml DMSO. The reaction was exothermic and cooling was required tomaintain the temperature below 70° during addition. After the additionwas complete heating was required to maintain the temperature at 60°-70°for 3.5 hours. The reaction mixture was allowed to cool to roomtemperature and then was poured into 600 ml H₂ O. This solution wasextracted with ether. The ethereal extracts were combined, washed withwater and saturated NaCl, and dried over CaSO₄. After removing the etheron a rotoevaporator 87.3g of red brown oil remained which contained 91%produce by glc. Vacuum distillation (120°-150°/0.05 mm Hg) gave theproduct as a colorless oil. 'Hnmr analysis was consistent with thestructure.

(c) Preparation of Trisodium 2,2,5-Tetrahydrofurantricarboxylate

To a warm solution of 64.1g of 50% NaOH in 200 ml H₂ O was added 60g ofthe product of Step (b) diluted with 20 ml ethanol. The solution wasinitially two phase but became homogeneous after stirring severalminutes. The solution was maintained at 60°-70° under a stream of N₂ for3 hours. The resulting yellow solution was poured into 450 ml MeOH. Anoil formed which on further workup under MeOH gave a yellow solid. Thesolid was dissolved in H₂ O and treated twice with charcoal. The paleyellow solution was treated repeatedly with ethanol until it solidified.The solid was washed with ether and dried overnight in a vacuum oven at80°. The solid was ground in a blender and dried an additional 3 hoursin the vacuum oven. The yield was 59g of off-white powder.

'Hnmr indicates some ethanol was still present as well as 1/2 mole H₂ O.Thermographic analysis showed a 5.9% weight loss up to 350° at whichpoint decomposition occurred. There appears to be a very thermallystable 1/2 hydrate which does not break down until about 250°. Glcanalyses of the salt indicated 84% of the trisodium2,2,5-tetrahydrofurantricarboxylate and 15% dicarboxylate. Dicarboxylateprobably resulted from decarboxylation of some of the tricarboxylateduring hydrolysis and/or charcoal treating. The divalent ion electrodetitration gave the following values: A=54 mV; B=37 mV; C=6.2 ml; D=7.4ml for an intensity-capacity index of 92% STP.

The salt appears to have a water solubility of slightly greater than 50%and when a 50% solution is allowed to evaporate, crystals of the productform. The solution could be evaporated to dryness and the product didnot appear to be hydroscopic. Purification by crystallization should bepossible.

EXAMPLE 4 Preparation of Trisodium 1,4-Dioxane-2,2,6-Tricarboxylate

Trisodium 1,4-dioxane-2,2,6-tricarboxylate and its esternitrileprecursor is prepared in the same manner as described in Example 1 fortrisodium 2,2,6-tetrahydropyrantricarboxylate except that Compound X:##STR20## is substituted for Compound V in Step (d) of Example 1.Compound X is prepared as follows: ##STR21##

A solution of 27g of (I) as described in A. Ya. Yakubovich and I.N.Belyreva, Zhur, Obshchei Khim. 31, 2119-22 (1961) CA: 56, 313e (1962) in25 ml tetrahydrofuran (THF) is added to a slurry of 2.4g of NaH in 100ml THF. When evolution of H₂ has ceased, 19.7g of II is added and themixture solution warmed to reflux temperature of the THF. The reactionmixture is refluxed until neutral. The solvent is removed on a rotaryevaporator. The residue is taken up in ether, washed with water andsaturated NaCl solution and dried over CaSO₄. The ether is removed on arotary evaporator leaving the crude product.

What is claimed is:
 1. A compound of the formula: ##STR22## wherein X isselected from the group of: ##STR23## wherein R is selected from thegroup consisting of alkali metal, NH₄ ⁺, NH(CH₂ CH₂ OH)₃ ⁺, and loweralkyl, branched or straight chain, with up to about C₂₀ in the chain. 2.A compound of claim 1 of the formula: ##STR24##